Lux is currently being hinted at being a lesbian thanks to her magical powers being framed as an allegory for being a gay teen. I personally think it's hamfisted and stupid, but it at least has more emotional weight than flat and pandering dynamic like Cait/Vi or Diana/Leona.
Additionally, making Elise a kind of sexual predator who feasts on the beauty of other women to keep herself young would help differentiate herself from Evelynn and Zyra (you could honestly say the same about Zyra, one of the other)>Gay
I unironically think that making Darius into pounding twink ass could actually help accentuate the hypermasculine macho vibe he has going on- in other words, the dude's so manly and obsessed with strength that women disgust him. Another good angle would be a guy who's torn between his sincere desire to uphold his duty to his family (and thus marry and reproduce to secure an heir) and his love for another man. The thing is, Garen already does that with a hetero relationship, and no other such male champion really exists right now.>Bi
Literally who cares. The only real story I could think of that's worth telling is a homosexual ex treating the bi person like a traitor for being in a het relationship, but that's not really something you can express in League.>Trans
Taliyah being born with a penis would explain her design perfectly